• Clinical science

Connective tissue diseases


Connective tissue is an important biological tissue composed of an extracellular matrix that binds, anchors, and supports organs. There are various types of connective tissue, all of which consist of varying combinations of fibers, cells, and intercellular substance. Over 200 conditions, which may be inherited or autoimmune, affect connective tissue, and they are collectively known as connective tissue diseases (CTDs). Inherited CTDs are caused by mutations that affect one of the two fibers (collagen and fibrillin). Autoimmune CTDs have no clear etiology, but the incidence is higher in women and among genetically predisposed individuals. As the name suggests, in autoimmune CTDs, the immune system develops antibodies against components of connective tissue. Individual conditions can affect a vast range of bodily structures (including cartilage, blood vessels, bone, tendons, and organs) and thus present with a wide array of clinical findings.

Autoimmune connective tissue diseases

Inherited connective tissue diseases


Clinical manifestations of connective tissue disorders

Clinical features vary greatly among individual diseases. The table below provides a general overview of the more common features.

Autoimmune CTDs Inherited CTDs
General features
  • Fever, weight loss, fatigue
  • Fatigue, weakness
Musculoskeletal symptoms
  • Joint hypermobility, curved spine, brittle bones, bone deformities, growth abnormalities (short or tall stature)
Skin manifestations
  • Hyperextensive, fragile skin
Organ manifestations


Connective tissue disorders

This table lists the most important connective tissue disorders and some examples of their clinical features. For more information on Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta, see the respective articles.

Condition Etiology Pathophysiology Clinical features (examples)
Marfan syndrome
Ehlers-Danlos syndrome
  • Defective collagen cross-linking and fibril synthesis
Menkes disease
  • X-linked recessive neurodegenerative disease caused by a mutation in the gene ATP7A (coding for Menkes protein, copper-transporting ATPase 1)
Osteogenesis imperfecta

The ATP7A gene is defective in Menkes disease, whereas the ATP7B gene is defective in Wilson's disease!

Ehlers-Danlos syndrome and Menkes disease are both associated with reduced lysyl oxidase activity, resulting in defective collagen cross-linking and fibril synthesis.